Abstract
Background/AimsHBV has been classified into ten genotypes (A–J) and multiple subgenotypes, some of which strongly influence disease outcome and their distribution also correlate with human migration. HBV infection is highly prevalent in India and its diverse population provides an excellent opportunity to study the distinctiveness of HBV, its evolution and disease biology in variegated ethnic groups. The North-East India, having international frontiers on three sides, is one of the most ethnically and linguistically diverse region of the country. Given the paucity of information on molecular epidemiology of HBV in this region, the study aimed to carry out an in-depth genetic characterization of HBV prevailing in North-East state of Tripura.MethodsFrom sera of chronically HBV infected patients biochemical/serological tests, HBV DNA quantification, PCR-amplification, sequencing of PreS/S or full-length HBV genomes were done. HBV genotype/subgenotype determination and sequence variability were assessed by MEGA5-software. The evolutionary divergence times of different HBV subgenotypes were estimated by DNAMLK/PHYLIP program while jpHMM method was used to detect any recombination event in HBV genomes.ResultsHBV genotypes D (89.5%), C (6.6%) and A (3.9%) were detected among chronic carriers. While all HBV/A and HBV/C isolates belonged to subgenotype-A1 and C1 respectively, five subgenotypes of HBV/D (D1–D5) were identified including the first detection of rare D4. These non-recombinant Indian D4 (IndD4) formed a distinct phylogenetic clade, had 2.7% nucleotide divergence and recent evolutionary radiation than other global D4. Ten unique amino acids and 9 novel nucleotide substitutions were identified as IndD4 signatures. All IndD4 carried T120 and R129 in ORF-S that may cause immune/vaccine/diagnostic escape and N128 in ORF-P, implicated as compensatory Lamivudine resistance mutation.ConclusionsIndD4 has potential to undermine vaccination programs or anti-viral therapy and its introduction to North-East India is believed to be linked with the settlement of ancient Tibeto-Burman migrants from East-Asia.
Highlights
The striking genetic heterogeneity displayed by HBV result mostly from copy errors introduced by viral polymerase during replication of its DNA genome through reverse transcription of pregenomic RNA [1]
Ten unique amino acids and 9 novel nucleotide substitutions were identified as Indian D4 (IndD4) signatures
IndD4 has potential to undermine vaccination programs or anti-viral therapy and its introduction to NorthEast India is believed to be linked with the settlement of ancient Tibeto-Burman migrants from East-Asia
Summary
The striking genetic heterogeneity displayed by HBV result mostly from copy errors introduced by viral polymerase during replication of its DNA genome through reverse transcription of pregenomic RNA [1]. Comparisons of HBV sequences from different geographical regions revealed the presence of ten genotypes (A–J), defined by genome dissimilarity by more than 7.5% and most genotypes further segregate into subgenotypes that differ from each other by 4–7.5% [1]. Genotype D (HBV/D) is most widespread and comprised of 9 subgenotypes (D1–D9), of which Primer Name. F1 F3 F4 F5 F7 F8 F10 R1 R2 R3 R5 R8 R9 SP2 MP1 MP2 P1y P2y Primer sequence. ** = nucleotide [nt] positions are given according to HBV sequence with accession no.
Sign-in/Register to view highlights & summary Talk to us
Join us for a 30 min session where you can share your feedback and ask us any queries you have
Schedule a callDisclaimer: All third-party content on this website/platform is and will remain the property of their respective owners and is provided on "as is" basis without any warranties, express or implied. Use of third-party content does not indicate any affiliation, sponsorship with or endorsement by them. Any references to third-party content is to identify the corresponding services and shall be considered fair use under The CopyrightLaw.
